Octenidine Dihydrochloride-impregnated socks for the treatment of onychomycosis: a randomized, double-blind, placebo-controlled pilot study

Onychomycosis (OM) is a fungal infection characterized by nail thickening and dystrophy1. Despite multiple treatments available3,4, the success rate remains relatively low5, with infection recurrence as high as 70%5. These poor outcomes may be, in part, explained by iatrogenic effects of medication, long duration of the treatment, costs associated, as well as self-care.5 Octenidine Dihydrochloride (OCT-D) is a low-cost antiseptic solution, with little side effects; and good efficacy against skin microflora7,8,9. Even though OCT-D has in vitro antifungal properties10, there is relatively scarce evidence on its efficacy in vivo. Here, we propose to: i) develop a new method to deliver OCT-D, using nanotechnology based Octenidine Dihydrochloride-impregnated washable socks. These will be developed by the team member, and private company, Barcelcom Têxteis. ii) conduct a pilot double blind randomized clinical trial approach to test the effects of OCT-D in OM patients. 20 outpatient participants from the Hospital das Forças Armadas (HFAR) will be randomized to a transdermal OCT-D solution release to socks (experimental) or no antiseptic solutions release to socks (placebo) groups. Both groups will wear the socks every day for 12 weeks (3 months) (Appendix 2). Participants will be instructed to follow a daily hygiene care protocol for assessing personal hygiene care and recording risk factors (e.g., type of footwear, nail cutting, etc.), through scheduling contacts via phone. The assigned participants will be assessed for clinical, dermoscopic, microbiological, neurological, neurophysiological, scales and questionnaires on quality of life, therapeutic regimen management and psychological profile in five different time periods (0, 1, 2, 3, 4 months) by evaluators blinded to group allocation. Assessing this information is relevant because, in addition to histology, PCR methods, Microscopy, and fungal culture 13, OM patients have been shown oxidative stress markers toward an imbalanced homeostasis14, which can be accessed via EEG 15,16. Furthermore, there is evidence outlining the biopsychosocial impact of OM (e.g., pain, quality of life, etc.)12. Aim iii) The large amount of data will be analyzed using Artificial Intelligence (Artificial neural networks) to highlight predictors of clinical outcomes.
In sum, our proposal has the potential to achieve a relevant advance in scientific knowledge while generating direct social benefits to our society.